The basic aim of this grant request is to study the relationship of oxygen supply and demand on a regional basis in the heart and other organs under control and stressful conditions. To this end we have developed a new and highly accurate microspectrophotometric method for determination of the oxygen saturation in small arteries and veins of a quick frozen tissue. By combining these measurements with a regional flow determination with radioactive microspheres, regional oxygen consumption can be calculated for the first time quantitatively. Such measurements are now proceeding in the heart. Most measurements will be performed on anesthetized open chest dogs and minipigs. The effects of the partial ischemia induced by graded flow reduction on regional myocardial oxygen consumption and relative open capillary density will be studied. The effects of increasing heart work through atrial pacing, valvular or supravalvular stenosis on the relation of myocardial oxgen supply to demand will be determined. Some studies of this sort will also be done in isolated perfused rabbit heart to obtain better quantitation of the exact relationships. Studies will be conducted of pharmacological agents that are of proposed utility in the treatment of infarction, coronary artery disease and angina pectoris to determine their effects on oxygen supply and demand on a regional basis in the heart. Studies will be conducted to determine the oxygen supply-demand relation in the brains of conscious cats to obtain this on a regional basis. The effects of hypoxia in normal and chemodenervated animal will be studied to determine those areas of the brain best protected. Measurement of oxygen saturation will be obtained from the blood vessels of the carotid bodies of anesthetized cats to determine if areas of differing saturation exist in euoxic or hypoxic conditions. In conscious guinea pigs, the relation of oxygen and glucose usage will be studied in normal and endotoxin shock animals. All of these studies will allow quantitative measurements to be obtained of regional oxygen consumption in different organs and under different conditions.